BACKGROUND: The objective was to evaluate the efficacy of a strong increase of the dose-intensity of concomitant radio-chemotherapy (RT-CT) in patients with far advanced non metastatic HNSCC.METHODS: Eligible patients had N3 disease (UICC 1997) and the primary tumor and/or the node(s) had to be strictly unresectable. Patients with palpable N2B-C were also eligible if massive nodal involvement was present. 109 patients were included, with 53 randomized to RT-CT and 56 to accelerated RT. In the RT-CT arm, the RT regimen consisted of 64Gy in 5weeks and the CT regimen consisted of synchronous CDDP 100mg/m(2) on days 2, 16, and 30 and 5FU 1000mg/m(2) on days1-5 and 29-33 of the RT course. After RT-CT, two adjuvant cycles of CDDP-5FU were delivered in good responders. A control arm was using a very accelerated RT, delivering 64Gy in 3weeks.RESULTS: The most common tumor sites were oropharynx and hypopharynx. Most of the patients had T4 disease (70%) and 100% had a massive nodal involvement (mainly N3 with a mean nodal size >7cm in both arms). A significant difference was observed in favor of the RT-CT arm (p=0.005) in terms of cumulative incidence of local regional failure or distant metastases. However, the overall survival and event free survival rates were not significantly different between the two arms (p=0.70 and 0.16, respectively). The lack of survival benefit in favor of the RT-CT was partly due to an excess of initial early treatment related death in the RT-CT arm.CONCLUSION: The very intense RT-CT schedule was more efficient on disease control, but was also more toxic than accelerated RT alone, pointing out that there was no clear improvement of the therapeutic index. This study shows the limits of dose-intensification, with regard to concomitant RT-CT.